Influence of adrenomedullin on tone of isolated bovine retinal arteries.
PURPOSE: To assess and characterize the vasorelaxing effect of adrenomedullin (AM) on isolated bovine retinal arteries (BRAs). METHODS: Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of AM (1 pM to 0.1 micro M) to the organ bath. RESULTS: AM caused a concentration-dependent relaxation of the BRAs. Removal of the endothelium of the BRAs, inhibition of nitric oxide synthase with -nitro-L-arginine (L-NA) or inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly reduced the AM response. Cyclooxygenase inhibition with indomethacin or sodium diclofenac did not reduce, but rather increased, vasodilation. The AM-receptor antagonist AM 22-52 slightly, but significantly, reduced the AM response, whereas the CGRP-receptor antagonist CGRP 8-37 caused a more pronounced reduction. The adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (8-SPT) did not affect AM-induced vasorelaxation. Inhibition of several intracellular calcium ([Ca(2+)](i))-reducing mechanisms failed to block the relaxation induced by AM. Only inhibition of the plasma membrane Ca(2+)-adenosine triphosphatase (ATPase) with vanadate significantly attenuated the AM response. CONCLUSIONS: AM induces vasodilation in isolated bovine retinal arteries. Endothelium-derived NO and stimulation of CGRP- and AM-receptors appear to be involved in the AM response, whereas prostanoids and activation of adenosine receptors are not involved. Activation of Ca(2+)-extrusion by the plasma membrane Ca(2+)-ATPase may elicit the relaxation of BRAs in response to AM.[1]References
- Influence of adrenomedullin on tone of isolated bovine retinal arteries. Boussery, K., Delaey, C., Van de Voorde, J. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
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